Sensorimotor gating in humans with tinnitus and hyperacusis

描述（由申请人提供）：这项研究耳鸣和听觉过敏患者感觉运动门控的经典指标--声惊吓反应（ASR）和前脉冲抑制（PPI）的建议既重要又及时。其动机是（i）几乎完全缺乏关于ASR或PPI与人类耳鸣或听觉过敏相关的数据，尽管这些措施在客观化和阐明各种其他状况方面取得了成功，这些状况也被认为涉及抑制和过度兴奋的失败，包括精神分裂症，强迫症和图雷特综合征，（ii）动物模型中增强的ASR表明听觉过敏，但缺乏数据测试这一假设，（iii）最近激增的兴趣，在一个缺口检测惊吓反射（GDSR）测试耳鸣的动物，这还有待验证，在人类和依赖于ASR和神经回路介导PPI。在人类受试者中测量ASR、PPI和GDSR的拟议实验将测试（1）对耳鸣和听觉过敏机制的见解是否可以从ASR和PPI已经被充分表征的其他更深入研究的神经学病症中得到利用，以及（2）被认为指示动物中的听觉过敏和耳鸣的ASR和GDSR测量是否实际上如此。拟议的工作是至关重要的了解临床耳鸣和听觉过敏，特别是，将其与动物数据的基础神经机制，这些日益普遍的疾病。

DESCRIPTION (provided by applicant): This proposal to examine classic indicators of sensorimotor gating - the acoustic startle response (ASR) and prepulse inhibition (PPI) - in humans with tinnitus and hyperacusis is both important and timely. It is motivated by (i) the almost complete absence of data on either ASR or PPI in relation to human tinnitus or hyperacusis, despite the success of these measures in objectifying and elucidating a variety of other conditions also thought to involve failures of inhibition and over-excitation, including schizophrenia, obsessive compulsive disorder and Tourette's syndrome, (ii) suggestions that enhanced ASR in animal models indicates hyperacusis, but a lack of data testing this hypothesis and, (iii) the recent surge of interest in a gap-detection startle reflex (GDSR) test fo tinnitus in animals, which has yet to be validated in humans and is reliant on the ASR and neural circuitry mediating PPI. The proposed experiments measuring ASR, PPI and GDSR in human subjects will test (1) whether insights into the mechanisms of tinnitus and hyperacusis might be leveraged from other more heavily studied neurological conditions for which the ASR and PPI are already well-characterized, and (2) whether ASR and GDSR measures thought to indicate hyperacusis and tinnitus in animals actually do. The proposed work is crucial to understanding clinical tinnitus and hyperacusis and, specifically, relating it to animal data on th underlying neural mechanisms of these increasingly prevalent disorders.